Toilet that detects fluorescent drug markers and methods of use thereof

ABSTRACT

The present disclosure describes a method of detecting a drug marker in urine a urine sample using a toilet. The drug markers are fluorophores each of which emits a unique fluorescence spectra. Accordingly, the method does not detect the drug but rather, the drug marker. The drug marker may include quantum dots which may be functionalized by connecting the quantum dot to a biomolecule. The biomolecule may be cleavable by a peptidase, a protease, or a nuclease to release the drug. Alternatively, the composition may include a liposome carrier. A user who has consumed the drug composition urinates into the toilet and a urine sample is captured. The toilet includes a mechanism for fluid handling which diverts urine into a fluorescence spectrometer. The fluorescence spectrometer screens the urine for drug markers based on their unique fluorescent spectra.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of co-pending U.S. patentapplication Ser. No. 15/361,872 filed on Nov. 28, 2016 which is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

This invention relates to devices for detecting and quantifying drugs ina user's bodily fluids or bodily waste and methods of use thereof.

BACKGROUND OF THE INVENTION

Detection of drugs after consumption is useful for many purposesincluding detection of illicit drug use, verification of prescriptiondrug consumption, detection of drug consumption to avoid potentialinterference from contraindicated drugs, monitoring pharmacokineticrates, dosage adjustment and many others. Drug testing typicallyinvolves urine or blood sampling, and in some cases saliva testing. Insome situations a quantitative measurement is needed while in others, aqualitative presence detection is sufficient.

Drugs may be detected in an individual's bodily fluids or bodily wasteby several methods. These include colorimetric assays, immunoassays,chromatography, and other chemical detection methods. Each of thesemethods is associated with its own limitations.

Convenient methods of drug detection and quantification includedetection of the drug or drug metabolite in urine or saliva. However,detection and measurement of a drug by colorimetric or immunoassaymethods typically requires development of a custom assay for eachchemical or biochemical target. This means that a detection assay mustbe developed specifically for each drug or class of drugs. Developing acustom assay limits drug detection to high risk drugs of abuse or verycommon drugs for which a large enough market exists. More specifically,the need for the assay must be worth the cost of developing the assay.Alternatively, separation and detection techniques, includingchromatography may be used. However, these techniques require complexlab equipment and calibration.

An alternative method to detect and/or quantify the presence of a drugin an individual's body is to put a marker in the drug, the markerhaving a detectable signature or characteristic. This techniquealleviates the need to directly measure the drug or the drugmetabolites. With this technique, the problem simplifies to developingmethods to detect the marker instead of the drug or drug metabolite.Because there are many available drugs, many different markers areneeded for to distinguish between different drugs. The markers may haveone or more distinguishing characteristic so that the identity of eachdrug may be determined and the simultaneous presence of multiple drugsmay be detected. Ideally, the markers may be biocompatible and notsignificantly biodegradable. They may have an easily detected signatureand not interfere with the efficacy of medically useful drugs. Forconvenience, the markers may be cleared from the body through urine.Markers that meet these specifications and a device to convenientlyidentify and quantify the markers in urine is needed.

SUMMARY

We disclose a novel method for inferring the identity and quantity ofdrugs consumed by a user by detecting a fluorescent drug marker in theurine of a user. The analytical instrument used in the method is atoilet into which the user urinates as the user would normally do whenusing a traditional toilet. This method provides a level of conveniencethat does not exist with traditional drug testing methods.

The method includes providing a user who consumes a composition whichincludes a drug and a fluorescent drug marker. Each fluorescent drugmarker possesses a unique fluorescence emission spectra and each drug iscompounded with a different drug marker. By detecting the fluorescenceemission spectra and matching it to the fluorescent signatures of knowndrug markers, the presence of the drug associated with that drug markermay be inferred.

The method further includes the use of a toilet which a user may easilyand conveniently urinate into, as when using a traditional toilet.However, the toilet disclosed herein is unique at least because itincludes a fluid handling system which collects a urine sample anddiverts it into a fluorescence spectrometer for analysis. Morespecifically, the fluid handling system transfers the urine sample froma urine capture reservoir to a fluorescence measurement cell. Thefluorescence measurement cell is a component of a fluorescencespectrometer that is within the toilet. The fluorescence spectrometerperforms the steps of directing a filtered light source of a definedwavelength or range of wavelengths into the fluorescence measurementcell. The drug marker in the urine sample absorbs the light and emitslight of a different wavelength. The fluorescence emission spectrum ismeasured and compared to known fluorescent signatures of the differentdrug markers in use.

The disclosed method identifies the drug the user consumed withoutdirectly measuring the drug itself or its metabolites. Measuring thefluorescence emission spectra of drugs in the urine replaces the need tomeasure the drug itself because each drug is compounded with a uniquefluorescent drug marker and because each unique drug marker emits adistinguishable fluorescent signature. This solution removes the need todevelop a new analytic tool for each drug. Applying the intensity of thefluorescent signals to standard curves further provides estimates of theamount of drug marker in the urine.

The toilet may further include one or more mechanisms for identifyingthe user. In some embodiments, the toilet may include a controllerconnected to the toilet which may link the measurements performed oneach user's urine to the user's identity. In this embodiment, the methodincludes the steps of actuating the user identification mechanism sothat the results of the urine analyses are stored in a file thatcollects that user's results. Repeated measurements may be collected andstored for multiple users with the results for each user readilyidentifiable. The controller may transfer stored data to a networkdatabase which may then be downloaded to a remote processor foranalysis. The data may be analyzed by healthcare provider, lawenforcement, and others for purposes that include determining whether auser is compliant in taking his or her medication, determining whetherthe user has accidentally consumed a drug in the wrong amount,determining whether a user has consumed drugs that are inappropriate ornot prescribed to that user, estimating the severity of a drug overdose,estimating pharmacokinetic properties of a drug, and detecting illicitdrugs in a user's body.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a cross sectional view of a toilet according to an embodimentof the invention.

FIG. 1B is a perspective view of a toilet according to an embodiment ofthe invention.

FIG. 1C is an aerial view of a toilet according to an embodiment of theinvention.

FIG. 2 is a schematic drawing of the components of the urine samplingand the fluorescence spectroscopy analysis systems according to anembodiment of the invention.

FIG. 3A is a schematic drawing of an embodiment of components of afluorescence spectroscopy analysis system.

FIG. 3B is a schematic drawing of an embodiment of components of afluorescence spectroscopy analysis system.

FIG. 3C is a schematic drawing of an embodiment of a urine samplingmechanism for loading urine into dual fluorescence measurement cells.

FIG. 4A is a schematic drawing of a rinsing device including a valveaccording to an embodiment of the invention.

FIG. 4B is a schematic drawing of a rinsing device including a pumpaccording to an embodiment of the invention.

FIG. 5 is a schematic drawing of a user on a toilet according to anembodiment of the invention illustrating embodiments of useridentification mechanisms.

FIG. 6 is a flow chart illustrating an embodiment of a method of usingthe disclosed invention.

DETAILED DESCRIPTION Definitions

Drug, as used herein, means a medication which may be used forlegitimate medical treatment, illicit bioactive substances which may ormay not have a legal and legitimate medical use, both prescription andnonprescription substances, and both natural and synthetic substances.The terms “medicine” and “medication” are included in the definition of“drug” as used herein. In some embodiments, the drug may be a smallmolecule. In other embodiments, the drug may be a peptide or antibody.

Toilet, as used herein, means a device that may be used to collect oneor more biological waste products of a user. This may include atraditional water toilet. However, toilet, as used herein, may mean anydevice which may be used to collect bodily waste according to thepresent disclosure and which may be equipped to analyze bodily wasteaccording to the present disclosure.

User, as used herein, means a human or animal that deposits bodily wasteinto an embodiment of the toilet disclosed herein.

Consumed, as used herein with regard to drugs, means oral, intravenous,intramuscular, intraperitoneal, sublingual, subcutaneous, transdermal,or nasal administration of the drug or any other route of administrationwhich would cause a drug to be metabolized in the body.

Disclosed herein is a method of identifying what drug or drugs a userhas consumed by measuring a fluorescent drug marker in the user's urine.The measurement is performed using a toilet equipped with a fluorescencespectrometer. The toilet used in the disclosed method comprises a fluidhandling system for collecting a urine sample as the user urinatesnormally into the toilet. The fluid handling system samples the user'surine and diverts it into a fluorescence spectrometer which may belocated on or within the toilet. The fluorescence spectrometer measuresthe fluorescence spectra emitted by one or more drug markers in theurine sample. The fluorescence signal may be proportional to the amountof drug that entered the user's body and which was cleared by the renalsystem. Therefore, not only may the presence of the fluorescent signalindicate that the user consumed the drug but the intensity of thefluorescent signal may be used to estimate the quantity of drugconsumed.

This system has a variety of uses including, but not limited to,determining whether a user is compliant in taking his or her medication,determining whether the user has accidentally consumed a drug in thewrong amount, determining whether a user has consumed drugs that areinappropriate or not prescribed to that user, estimating the severity ofa drug overdose, estimating pharmacokinetic properties of a drug, anddetecting illicit drugs in a user's body.

The fluorescent signal may be generated by a fluorescent marker mixedwith or connected to the drug to form a composition. The drug may beconnected to the fluorescent marker through a variety of mechanisms.These include covalent or noncovalent bonding and encapsulating the drugin a carrier that emits a fluorescent signal before or after releasingthe drug from the carrier.

An example of a carrier is a clathrate containing a fluorescent marker.According to the disclosure, the clathrate may be a lattice “cage” thattraps the drug inside. The clathrate lattice may comprise thefluorescent molecule or the fluorescent molecule may be inside theclathrate lattice. In some embodiments, the clathrate is a nanodiscclathrate.

In other embodiments, the carrier may comprise a liposome. The drug maybe inside the liposome. In some embodiments, more than one drug isinside the liposome. In some embodiments, the fluorescent drug marker isin the center of the liposome along with the drug. In other embodiments,the fluorescent drug marker is part of the liposome's lipid layer.Fluorescent molecules that have hydrophobic properties may be optimallyincorporated in the liposome's lipid layer whereas more hydrophilicfluorescent markers may be optimally placed in the center of theliposome.

In some embodiments, the liposome may include ligands which target theliposome to a specific tissue. The specific tissue may be a tissue whichis the target of the drug. Consequently, the liposome delivers the drugto the tissue with which the drug is intended to interact.

Another drug marker candidate is a quantum dot, a nanoscalesemiconductor with size-dependent fluorescence emission. The quantum dotmarker may be suitable for consumption and may be synthesized andsolubilized with sufficient homogeneity to create quantum dot solutionswith many different fluorescence emission bands for use as drug markers.

Quantum dots may be passivated, functionalized, or encapsulated toachieve a relatively chemically inert fluorescence marker. The quantumdot solutions may include the drug, or in some embodiments, the quantumdot may be encapsulated or functionalized with biomolecules by coatingthe quantum dot to a biomolecule. The biomolecule may include ahydrogel, a protein, a peptide, a DNA molecule, an RNA molecule, or anantibody. In some embodiments, the DNA molecule comprises a non-genomicDNA sequence and/or a non-naturally occurring peptide sequence. Inembodiments where the quantum dot is functionalized and/or encapsulatedusing a DNA molecule, the DNA molecule may include one or morenucleotide cleavage sites. The nucleotide cleavage sites may be cleavedby a nuclease and the drug released. In some embodiments, the nucleotidecleavage site may be a restriction endonuclease cleavage site. Becauserestriction endonucleases are produced by bacteria, in some embodimentsthe bacteria in the user's gastrointestinal tract may cleave the DNAmolecule at the restriction endonuclease cleavage site causing the drugto be released. The drug may then be absorbed by the intestine andperform its intended biological function on the user leaving the drugmarker to be cleared by the renal system and measured in urine.

In some embodiments in which the quantum dot may be functionalized orencapsulated by a DNA molecule or RNA molecule, the DNA or RNA moleculemay be cleaved by a eukaryotic nuclease. In some embodiments, the DNA orRNA may be single stranded and cleaved by a eukaryotic single strandnuclease. Examples of eukaryotic single strand nuclease which may becleave the single stranded DNA or RNA according to the disclosureinclude zinc finger nuclease, RNAse H2, pancreatic nuclease, and p53.

In some embodiments, the DNA molecule may be double stranded and cleavedby a eukaryotic double strand nuclease including DNAse I.

In embodiments in which the quantum dot is functionalized orencapsulated by a protein or peptide, the protein or peptide may includea protease cleavage site. Endogenous proteases that are present in theuser's body may cleave the protein or peptide at the protease cleavagesite. The drug may then be released and perform its intended biologicalfunction. In embodiments in which the quantum dot includes an antibody,the antibody may also include a peptidase cleavage site which may becleaved as described above.

In some embodiments, the protease cleavage site is cleaved by aeukaryotic protease produced by the user's body. In some embodiments,the eukaryotic protease may be a metalloprotease, a serine protease, ora digestive protease. Metalloproteases and serine proteases are found inmammalian blood and function in the management of thrombosis. Examplesof serine proteases in blood include thrombin, plasmin, and urokinase.In embodiments in which the protease cleavage site is cleaved by ametalloprotease or serine protease, the drug and fluorescent drug markermay be released into the user's blood.

Digestive proteases may be found in the stomach. They may function todirectly digest food or to activate proteins that assist ingastrointestinal function. Examples of digestive proteases includegastrin, pepsin, trypsin, and chymotrypsin.

In some embodiments, the quantum dot is functionalized and/orencapsulated with a peptide or protein and the peptide or protein isbound to a nucleotide sequence. The peptide, protein, DNA, or both maybe cleaved by appropriate enzymes to release the drug.

In some embodiments, the biomolecule is cleaved by a glycosidehydrolase. Lysozyme is an example of a glycoside hydrolase. Lysozymefunctions in mammals as an antimicrobial enzyme and is found in secretedfluids as well as in macrophages and polymorphonuclear neutrophils.

Mammalian bodies include prokaryotic cells which produce enzymes whichmay cleave the biomolecules according to the disclosure. For example,the colon includes the bacteria Escherichia coli (E. coli). Enzymesproduced by E. coli include nucleases, including exonuclease I,exonuclease IV, RNAse A, and RNAse I.

In some embodiments, the biomolecule includes a hydrogel. In someembodiments, the hydrogel comprises more than one drug. The hydrogel maybe cleaved in a low pH solution to release the drug and the fluorescentdrug markers. In some embodiments, the hydrogel may be cleaved in asolution that has a pH of between about 1.0 and about 3.0. An example ofa bodily solution which may be within this pH range includes gastricsecretions. Consequently, the drug and fluorescent drug marker may bereleased in the stomach.

The fluorescent drug molecule may be separated from the drug after thebiomolecule is cleaved as described above. The DNA, RNA, peptide,antibody, or other biomolecule may be engineered to include the desiredcleavage site. For example, the DNA molecule used to functionalize thequantum dots may be a non-genomic sequence that includes a restrictionenzyme cleavage site. Alternatively, in embodiments in which a peptideis used to functionalize the quantum dots, the peptide sequence may be anon-naturally occurring peptide sequence into which a peptidase cleavagesite has been engineered. While the newly released drug may bemetabolized to one or more byproducts that are difficult to measure, thefluorescent marker may be cleared by the urine independent from the drugand its metabolites. Consequently, the drug marker may be detected bythe fluorescent spectrometer in or on the toilet regardless of the fateof the drug molecule.

The markers in different drugs may have one or more distinguishingcharacteristic, including different fluorescence emission spectra, sothat the drug marker may be identified and distinguished from markersassociated with drugs. Consequently, in situations when a user hasconsumed more than one drug, the unique fluorescent signal of each drugmay enable quantification of each individual drug in the presence of theother drugs. Furthermore, the markers may be used in combination tobuild a unique code which identifies the combination of drugs consumedby a user and their respective quantities. Multivariate analysis may beused to disambiguate the signatures of multiple drugs.

The disclosure describes a mechanism for rinsing the fluid handlingsystem and fluorescence measuring cell after each use to prevent crosscontamination of samples. As described in more detail below, the rinsingdevice flushes water from a water source through the fluorescencemeasuring cell and through the fluid handling system up to the orificein the urine capture reservoir. The rinsing device may include a valve,a pump, or both to regulate water from the water source.

The disclosure includes mechanisms for user identification. The toiletmay identify the user as the user approaches through a wireless systemwhich may be the user's mobile device. Alternatively, the user may siton, or otherwise interact with the toilet which may take biologicalmeasurements, including body weight, blood pressure, or bioimpedancemeasurement, which may be unique to the user and thereby identify theuser. A user may also manually enter identification information whichmay comprise entering a code into a key pad to identify the user. Byidentifying each user, a controller that may be included in the toiletmay associate the results of the urine analysis with the user whoprovided the urine sample.

A controller in or connected to the toilet may record fluorescentmeasurements. In embodiments which include a mechanism to identify theuser, the controller may associate each user with the data collectedfrom that user's urine. The data may be uploaded to a network eitherwirelessly, through an Ethernet, or through other mechanisms known inthe art. The data may then be downloaded to a computer at a remotelocation for further analysis and use.

The disclosure includes a method for detecting at least one drug markerin a user's urine after the user has consumed a composition. The methodincludes the steps of administering a composition to the user whichincludes a drug and a fluorescent drug marker as described herein. Thefluorescent drug marker may emit a unique fluorescence emission spectrarelative to other fluorescent drug markers that may be present incompositions that include other drugs when exposed to light of a definedwavelength. The method includes the step of providing a toilet thatincludes a urine capture reservoir and a fluorescence spectrometer. Thefluorescence spectrometer may include one or more light sources, one ormore fluorescence measurement cells, and a spectral analyzer. The urinecapture reservoir may be connected to the fluorescence measurement cellsin the fluorescence spectrometer by a channel. Urine may travel throughthe channel from the urine capture reservoir to the fluorescencemeasurement cell where it is spectral properties are analyzed.

In some embodiments, the method uses a toilet that includes acontroller. The controller may include a connected to the fluorescencespectrometer and include a non-transitory computer readable medium forprocessing the data collected by the fluorescence spectrometer.

The method further includes the step of depositing the urine sample inthe toilet. The toilet may comprise of embodiments disclosed herein. Theuser may urinate into the toilet normally as with a traditional toilet.This step provides a level of convenience that is not available withother methods of assessing drug use. The fluorescence spectrometer maythen be actuated. In some embodiments, the controller actuates thefluorescent spectrometer. The fluorescence spectrometer then exposes theurine sample within the fluorescence measuring cell to light of thedefined wavelength and collects a fluorescence emission spectra readingfrom the urine specimen. The spectral analyzer then analyzes thefluorescence emission spectra reading.

The fluorescence emission reading may then be transferred to thecontroller. Non-transitory computer readable medium within thecontroller may identify the drug by comparing the fluorescence emissionspectra reading with the unique fluorescence emission spectra of knowndrug markers. Upon matching the fluorescence emission spectra readingwith that of a known drug marker, the controller may determine theidentity of the drug marker. The identity of the drug marker may beextrapolated to determine the identity of the drug.

The non-transitory computer readable medium within the controller mayalso perform the step of quantifying the fluorescent drug marker. Thismay be accomplished by applying the intensity of the fluorescenceemission spectra reading to a standard curve for the fluorescent drugmarker that is stored in the controller. By quantifying the fluorescentdrug marker in the urine sample, the amount of drug the user hasconsumed may be estimated.

It will be readily understood that the components of the presentinvention, as generally described and illustrated in the Figures herein,could be arranged and designed in a wide variety of differentconfigurations. Thus, the following more detailed description of theembodiments of the invention, as represented in the Figures, is notintended to limit the scope of the invention, as claimed, but is merelyrepresentative of certain examples of presently contemplated embodimentsin accordance with the invention. The presently described embodimentswill be best understood by reference to the drawings, wherein like partsare designated by like numerals throughout.

Referring to FIG. 1A, toilet 100 is an embodiment of the disclosedtoilet. Similar to traditional toilets, toilet 100 includes seat 110,lid 120, and toilet bowl 130. Toilet 100 further includes urine capturereservoir 140 which is shown in FIG. 1A as a raised mound. The mound ofurine capture reservoir 140 is a protrusion of the inner surface oftoilet bowl 130. The mound creates a ledge for capturing urine which, inthe absence of the mound, would fall directly into the toilet water orrun down the relatively vertical sides of the toilet bowl. In someembodiments, urine capture reservoir 140 is positioned near the front ofthe toilet relative to the user which is on the side of the toilet bowlthat is furthest from the trap.

FIG. 1A further illustrates depression 145 on the upper side of themound of urine capture device 140. Depression 140 allows urine flowingover the mound to pool for a short time and enter the urine analysissystem through orifice 150 (first presented in FIG. 1B).

In some embodiments, the urine capture reservoir includes a urinedetection sensor which detects urine in the urine capture reservoir. Theurine detection sensor may be connected to a controller which actuatesthe fluorescence spectrometer when urine is present in the urine capturereservoir. Examples urine detection sensors include, but are not limitedto, optical sensors and thermal sensors.

FIG. 1B illustrates toilet 100 with an illustration of orifice 150 onthe upper surface of urine capture device 140. In the embodiment of FIG.1B, orifice 150 is shown as a slit. The slit may be constructed of twoplates of glass positioned close together such that urine may be drawnthrough orifice 150 and into the urine analysis system by capillaryaction. In some embodiments, the length of the slit may range fromapproximately 2.5 mm to approximately 25 mm, or from approximately 2.5mm to approximately 9.5 mm. In one embodiment, the length of the slit isabout 6.35 mm. The height of the slit may, in some embodiments, rangefrom approximately 2.5 mm to approximately 31.75 mm. In one embodiment,the height of the slit is approximately 6.35 mm. In some embodiments,the width of the slit may range from approximately 0.5 mm toapproximately 2 mm. In some embodiments, the width of the slit may rangefrom approximately 0.75 mm to approximately 1.5 mm. In some embodiments,the width of the slit is approximately 1 mm. In other embodiments, theorifice is not a slit or is a slit but is not narrow enough to drawurine in through capillary action. In these embodiments, urine may enterthe orifice by gravitational action or by the action of a pump. The pumpmay be a syringe pump, a peristaltic pump, or other pump for movingliquid that is known in the art.

FIG. 1C is a view of toilet 100 from the viewpoint of a user lookingdown towards toilet bowl 130. Orifice 150 is shown as a slit on theupper surface of the mound of urine capture device 140. In thisembodiment, urine capture device 140 is positioned near the front of thetoilet bowl furthest from the trap. A user urinates into toilet bowl 130and onto urine capture device 140. Urine that flows over urine capturedevice 140 is delayed long enough for a sample to enter orifice 150through one of the mechanisms described above.

FIG. 2 illustrates a cross section of an embodiment of toilet 100.Orifice 150 leads into channel 250 which continues into fluorescencemeasurement cell 260 of a fluorescence spectrometer. Urine travels intoorifice 150, through channel 250, and into fluorescence measurement cell260 for analysis. In contrast, some embodiments include a section of thefluid handling system which functions as a fluorescence measurementcell. These embodiments include optical windows within the fluidhandling system and below the orifice (shielded from ambient light)through which fluorescent signal may be measured in the same or similarmanner as may be performed using the fluorescence measurement cell.

In some embodiments, the fluorescence measurement cell includes athermal regulator. The thermal regulator makes it possible to detectcertain temperature sensitive markers, a feature which adds anadditional method through which to identify the presence differentdrugs. In addition, the thermal regulator may reduce the temperature toimprove fluorescence emission quantum efficiency or achieve line-widthnarrowing. The thermal regulator may be connected to a controller whichregulates the temperature within the fluorescence measurement cell.

FIG. 2 further illustrates fluorescence excitation light source 280which emits light at multiple wavelengths. In some embodiments,fluorescence excitation light source 280 is a fluorescence pump lightsource. The fluorescence pump light source may be an ultraviolet laser,an ultraviolet light emitting diode (LED), or other fluorescence pumplight sources known in the art. As will be described in more detailbelow, the multiple wavelengths are filtered before enteringfluorescence measurement cell 260.

FIG. 2 also illustrates fluorescence spectral analyzer 270 which maydetect dispersed (special or time domain) or filtered light.Fluorescence spectral analyzer 270 may conduct a multichannel ormulti-element time or frequency domain analysis of the spectrum withsufficient resolution to detect multiple fluorophores. Examples includea compact optical grating spectrometer, a compact optical detectedFourier transform spectrometer, and a Michelson interferometer styleFourier transform spectrometer. Spectral analyzers may include abandpass filter array, a tunable filter, and variations thereof known inthe art. The spectral sensing band may be in the region 400-800 nmwavelengths, though it may extend to longer and shorter wavelengths. Theresolution may be desirably approximately than 30 nm wavelengths, orless than 15 nm wavelengths, or less than 10 nm wavelengths. Betterresolution allows for more independent fluorescence emission channels,down to the limit of the marker emission wavelength variation, which mayintrinsic, environmental, or due to polydispersity. In some embodiments,the fluorescence spectrometer performs an ensemble measurement of manydispersed markers in the optical region. In some embodiments, the toilethas a detector for detecting the dispersed (spatial or time domain) orfiltered light.

In some embodiments, the fluorescence measurement cell resembles that ofa flow cytometer. Specifically, urine passes through a microfluidicchannel of dimensions that may be approximately 100 microns in width. Insome embodiments, the width is with a range of between approximately 10microns and approximately 1000 microns. In some embodiments thatcomprise a microfluidic chamber, the fluorescence spectrometer maydetect one fluorescent marker at a time. An ensemble distribution iscreated as a plurality of markers are analyzed serially. This techniquehas the advantage of measuring markers with more than one emission peak,including overlapping peaks, since measuring multiple markers in anensemble measurement that is not performed by serial measurements wouldotherwise be ambiguous.

FIG. 2 also illustrates rinsing device 290 which is connected to tubing295. Rinsing device 290 is connected to a water source through tubing295. In some embodiments, the water source is refill water from thetoilet tank. Rinsing device 290 diverts water from the water sourcethough fluorescence measurement cell 260, channel 250, and orifice 150.This process removes residual urine from the system so that the nextuser's urine sample is not contaminated by that from the previous user.Rinse water from under the toilet rim as may be found in traditionaltoilets may also rinse the mound of urine capture device 140 so that auser's own urine stream does not wash urine from the previous user intoorifice 150 causing contamination.

FIG. 3A illustrates an embodiment of a fluorescence spectrometeraccording to the disclosure in more detail. Fluorescence excitationlight source 280 which emits light at multiple wavelengths which aredirected toward a first filter 310. First filter 310 blocks outapproximately all wavelengths of light except for those in a definedrange or of a defined wavelength, the defined range or wavelengthdepending on the fluorescent marker to be measured. The filtered lightthen passes through fluorescence measurement cell 260, thereby excitingfluorescent markers in the urine that are excitable by light of thedefined wavelengths. The fluorescent markers then emit fluorescent lightof a certain wavelength(s). The emitted fluorescent light travelsthrough second filter 320 which filters out approximately allwavelengths of light except for those to be measured. In this way, thewavelength of emitted fluorescent light that a marker associated with aparticular drug may be measured by fluorescence spectral analyzer 270without interference by signals from other markers.

FIG. 3B illustrates a second embodiment of a fluorescence spectrometeraccording to the disclosure which includes the components of thefluorescence spectrometer shown in FIG. 3A. The embodiment of FIG. 3Bfurther includes third filter 370 which functions analogous to firstfilter 310, a second fluorescence measurement cell 260. The embodimentof FIG. 3B further includes fourth filter 380 which functions analogousto second filter 320. Partition 390 divides the two sets of filters andthe two fluorescence measurement cells so that stray light form onesystem is not detected by the other system. Emitted fluorescent lightfrom each of fluorescence measurement cells 260 and 360 may be detectedby a spectral analyzer (for clarity, not shown). The spectral analyzermay sequentially measure the emissions from fluorescence cells 260 and360 or may be designed to simultaneously detect multiple fluorescenceemissions with filters or partitions in place to prevent stray lightcrossing over from the two fluorescence measurement cells.

FIG. 3C illustrates an embodiment of a urine capture reservoir and afluid handling system that diverts urine into two fluorescencemeasurement cells which may be the system illustrated in FIG. 3B. Theembodiment of FIG. 3C includes orifice 150 through which urine travelsinto chamber 310. Chamber 310 then divides into two branches, branch 315a and 315 b. Urine travels through branch 315 a into fluorescencemeasurement cell 360 and urine travels through branch 315 b intofluorescence measurement cell 380. Markers in the separated urine samplemay be analyzed as described in the discussion of FIG. 3B or otherembodiments thereof.

FIGS. 4A and 4B illustrate two different embodiments of the rinsingdevice. FIG. 4A illustrates an embodiment of the rinsing device whichincludes valve 290. In this embodiment, valve 290 is positioned withinthe rinsing device between the water source and the fluorescencemeasurement cell 260. Valve 290 may open and close tubing 295 which isconnected to the water source. In the embodiment shown in FIG. 4A, valve290 is connected to controller 410 through connector 420. Controller 410controls the opening and closing of valve 410 so that it is closed whenthe urine is being analyzed and opened after analysis is complete and itis time to flush out the system.

FIG. 4B illustrates another embodiment of the rinsing device whichincludes a pump 430. In this embodiment, pump 430 is a peristaltic pumpwhich is connected to controller 410 by connector 425. Controller 410actuates pump 430 to direct water from the water source through tubing295 after an analysis of urine is complete to rinse out the systembefore the next user. Controller 410 stops pump 430 during analysis ofurine. Some embodiments include both a pump and a valve in the rinsingdevice. Furthermore, some embodiments may include other types of pumpsknown in the art.

FIG. 5 illustrates user 520 in the process of urinating in toilet 510which is an embodiment of the disclosure. Toilet 510 includes multiplemechanisms for detecting a user's identity. User 520 is holding mobiledevice 530. Mobile device wirelessly communicates with controller 540 toprovide the controller with the user's identity. The wavy lineconnecting mobile device 530 with controller 540 represents the wirelesssignal.

In addition, toilet 510 includes keypad 560 which is also connected tocontroller 540 through wiring 570. User 520 could enter a keycode intokeypad 560 to provide identity information which is then transferred tocontroller 540. By providing user identity information, toilet 510 maycollect multiple analyses and assign each to the user who provided theurine sample.

In addition to a user's mobile device or a keypad, other embodiments ofthe disclosed toilet may use other methods to identify a user. Someembodiments may use biometric verification methods, includingfingerprint, iris, facial recognition, voice recognition, orelectrocardiogram readings. Alternatively, the toilet may identify theuser by unique user health signatures including measurement of bodyweight, bio-impedance, or urine flow rate.

In some embodiments, the controller is connected to a network database.Data collected by the toilet, along with associated user identityinformation, may be uploaded from the controller in the toilet to thenetwork database. Uploading may be performed wirelessly, through anEthernet, or other methods known in the art. The data may then bedownloaded to a computer at a remote location for analysis. The analysismay be performed by a healthcare provider, law enforcement in the caseof screening for illicit drugs, investigators conducting medicalstudies, or others who may have use for the data. In these embodiments,the controller within the toilet includes a data communication port.

FIG. 6 is a flow chart illustrating one embodiment of a method of usingthe disclosed toilet. In this embodiment, the toilet is equipped with aproximity detector which, upon detecting the presence of a user, alsoprovides user identity data. The proximity detector identifies the useras the user approaches the toilet. The user then urinates in the toiletand at least some of the urine is collected by the urine capturereservoir. Some of the urine enters the fluorescence measurement cellthrough the orifice in the urine capture reservoir. The fluorescencespectrometer measures the fluorescence emissions from drug markers inthe user's urine. The data is transferred to the controller where it maybe processed to identify and or quantify the drug marker and then to anetwork database. The fluorescence data is then downloaded to a remotecomputer for analysis to assess the user's drug consumption. Thefluorescence emission spectrum reading may be associated with the uniquefluorescence emission spectra of a known drug marker. Thus, the identityof the drug may be associated with the identity of the drug marker.

While specific embodiments have been described above, it is to beunderstood that the disclosure provided is not limited to the preciseconfiguration, steps, and components disclosed. Various modifications,changes, and variations apparent to those of skill in the art may bemade in the arrangement, operation, and details of the methods andsystems disclosed, with the aid of the present disclosure.

Without further elaboration, it is believed that one skilled in the artcan use the preceding description to utilize the present disclosure toits fullest extent. The examples and embodiments disclosed herein are tobe construed as merely illustrative and exemplary and not a limitationof the scope of the present disclosure in any way. It will be apparentto those having skill in the art that changes may be made to the detailsof the above-described embodiments without departing from the underlyingprinciples of the disclosure herein.

We claim:
 1. A method for detecting at least one drug marker in urinecomprising the steps of: providing a toilet, the toilet comprising: aurine capture reservoir, a fluorescence spectrometer, the fluorescencespectrometer comprising: at least one fluorescence excitation lightsource, at least one fluorescence measurement cell, and a spectralanalyzer; a channel, wherein the channel fluidly connects the urinecapture reservoir to the at least one fluorescence measurement cell; acontroller, the controller comprising a non-transitory computer readablemedium and, wherein the controller is connected to the fluorescencespectrometer; depositing a urine sample produced by a user's body intothe toilet, wherein at least a portion of the urine sample enters theurine capture reservoir, travels through the channel, and enters the atleast one fluorescence measurement cell, wherein the user has consumed acomposition, wherein the composition comprises at least one drug, atleast one fluorescent drug marker, and a liposome carrier, wherein theat least one drug is encapsulated within the liposome carrier, whereinthe at least one fluorescent drug markers emits a unique fluorescenceemission spectra relative to other fluorescent drug markers when exposedto light of a defined wavelength.
 2. The method of claim 1, wherein thefluorescent drug marker is encapsulated in the liposome carrier.
 3. Themethod of claim 2, wherein the liposome comprises a ligand, and whereinthe ligand targets a tissue in which is a target of the drug.
 4. Themethod of claim 1, wherein the composition comprises a plurality ofdrugs.
 5. The method of claim 1, wherein the toilet consists of a devicefor a deposition of human or animal waste.
 6. A method for detecting atleast one drug marker in urine comprising the steps of: providing atoilet, the toilet comprising: a urine capture reservoir, a fluorescencespectrometer, the fluorescence spectrometer comprising: at least onefluorescence excitation light source, at least one fluorescencemeasurement cell, and a spectral analyzer; a channel, wherein thechannel fluidly connects the urine capture reservoir to the at least onefluorescence measurement cell; depositing a urine sample produced by auser's body into the toilet, wherein at least a portion of the urinesample enters the urine capture reservoir, travels through the channel,and enters the at least one fluorescence measurement cell, wherein theuser has consumed a composition, wherein the composition comprises atleast one drug, and at least one quantum dot, wherein the at least onequantum dot is functionalized by coating or connecting the at least onequantum dot to a biomolecule, wherein the biomolecule is cleavable by apeptidase, a protease, or a nuclease, wherein the at least one quantumdot emits a unique fluorescence emission spectra relative to otherfluorescent drug markers when exposed to light of a defined wavelength.7. The method of claim 6, wherein the biomolecule is cleavable by aeukaryotic single strand DNA nuclease.
 8. The method of claim 7, whereinthe eukaryotic single strand nuclease is selected from the groupconsisting of a zinc finger nuclease, RNAse H2, pancreatic nuclease, andp53.
 9. The method of claim 6, wherein the biomolecule is cleavable byDNAse I.
 10. The method of claim 6, wherein the biomolecule is cleavableby a eukaryotic protease.
 11. The method of claim 9, wherein theeukaryotic protease is selected from the group consisting of ametalloprotease, a serine protease, a digestive protease.
 12. The methodof claim 11, wherein the digestive protease is selected from the groupconsisting of gastrin, pepsin, trypsin, and chymotrypsin.
 13. The methodof claim 11, wherein the serine protease is selected from the groupconsisting of thrombin, plasmin, and urokinase.
 14. The method of claim6, wherein the biomolecule is cleavable by a glycoside hydrolase. 15.The method of claim 14, wherein the glycoside hydrolase consists oflysozyme.
 16. The method of claim 6, wherein the biomolecule iscleavable by an enzyme derived from Escherichia coli.
 17. The method ofclaim 16, wherein the enzyme derived from Escherichia coli is selectedfrom the group that consists of exonuclease I, exonuclease IV, RNAse A,and RNAse I.
 18. The method of claim 6, wherein the biomoleculecomprises a hydrogel.
 19. The method of claim 18, wherein the hydrogelis cleaved by a solution comprising a pH of between about 1.0 and about3.0.
 20. The method of claim 6, wherein the composition comprises aplurality of drugs.